{"id":"https://openalex.org/W2012778393","doi":"https://doi.org/10.1248/bpb.28.124","title":"Identification of Cytochrome P450 Enzymes Involved in the Metabolism of FK228, a Potent Histone Deacetylase Inhibitor, in Human Liver Microsomes","display_name":"Identification of Cytochrome P450 Enzymes Involved in the Metabolism of FK228, a Potent Histone Deacetylase Inhibitor, in Human Liver Microsomes","publication_year":2005,"publication_date":"2005-01-01","ids":{"openalex":"https://openalex.org/W2012778393","doi":"https://doi.org/10.1248/bpb.28.124","mag":"2012778393","pmid":"https://pubmed.ncbi.nlm.nih.gov/15635176"},"language":"en","primary_location":{"id":"doi:10.1248/bpb.28.124","doi":"https://doi.org/10.1248/bpb.28.124","is_oa":true,"landing_page_url":"https://doi.org/10.1248/bpb.28.124","pdf_url":"https://www.jstage.jst.go.jp/article/bpb/28/1/28_1_124/_pdf","source":{"id":"https://openalex.org/S165235614","display_name":"Biological and Pharmaceutical Bulletin","issn_l":"0918-6158","issn":["0918-6158","1347-5215"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","jufo-1","medline","norway-1","poland-70","russia-white-list-2"],"host_organization":"https://openalex.org/P4310313382","host_organization_name":"Pharmaceutical Society of Japan","host_organization_lineage":["https://openalex.org/P4310313382"],"host_organization_lineage_names":["Pharmaceutical Society of Japan"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biological and Pharmaceutical Bulletin","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://www.jstage.jst.go.jp/article/bpb/28/1/28_1_124/_pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5030088283","display_name":"Toshifumi Shiraga","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Toshifumi Shiraga","raw_affiliation_strings":["Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5087074582","display_name":"Zenzaburo Tozuka","orcid":"https://orcid.org/0000-0002-2567-6416","observed_orcids":["https://orcid.org/0000-0002-2567-6416"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Zenzaburo Tozuka","raw_affiliation_strings":["Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012022945","display_name":"Rika Ishimura","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rika Ishimura","raw_affiliation_strings":["Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054696863","display_name":"Akio Kawamura","orcid":"https://orcid.org/0000-0003-3482-8853","observed_orcids":["https://orcid.org/0000-0003-3482-8853"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Akio Kawamura","raw_affiliation_strings":["Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5068340697","display_name":"Akira Kagayama","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Akira Kagayama","raw_affiliation_strings":["Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Ltd","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":1.335,"has_fulltext":true,"cited_by_count":38,"citation_normalized_percentile":{"value":0.76357388,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":97},"biblio":{"volume":"28","issue":"1","first_page":"124","last_page":"129"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.9970999956130981,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.0006000000284984708,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":0.0003000000142492354,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/romidepsin","display_name":"romidepsin","score":0.9850000143051147},{"id":"https://openalex.org/keywords/depsipeptides","display_name":"depsipeptides","score":0.9959999918937683},{"id":"https://openalex.org/keywords/histone-deacetylase-inhibitors","display_name":"histone deacetylase inhibitors","score":0.9629999995231628},{"id":"https://openalex.org/keywords/cytochrome-p450","display_name":"cytochrome P450","score":0.9160000085830688},{"id":"https://openalex.org/keywords/cyp3a4","display_name":"CYP3A4","score":0.8899999856948853},{"id":"https://openalex.org/keywords/cyp3a5","display_name":"CYP3A5","score":0.9990000128746033},{"id":"https://openalex.org/keywords/drug-metabolism","display_name":"drug metabolism","score":0.8999999761581421},{"id":"https://openalex.org/keywords/human-liver-microsomes","display_name":"human liver microsomes","score":0.9200000166893005},{"id":"https://openalex.org/keywords/testosterone-6beta-hydroxylase","display_name":"testosterone 6beta-hydroxylase","score":0.8539999723434448},{"id":"https://openalex.org/keywords/ketoconazole-inhibition","display_name":"ketoconazole inhibition","score":0.9240000247955322},{"id":"https://openalex.org/keywords/drug-drug-interactions","display_name":"drug-drug interactions","score":0.5120000243186951},{"id":"https://openalex.org/keywords/metabolites","display_name":"metabolites","score":0.3490000069141388}],"concepts":[{"id":"https://openalex.org/C109650736","wikidata":"https://www.wikidata.org/wiki/Q424440","display_name":"CYP3A4","level":4,"score":0.7443139553070068},{"id":"https://openalex.org/C87644729","wikidata":"https://www.wikidata.org/wiki/Q547502","display_name":"Microsome","level":3,"score":0.6827328205108643},{"id":"https://openalex.org/C2776202225","wikidata":"https://www.wikidata.org/wiki/Q3569101","display_name":"Histone deacetylase inhibitor","level":5,"score":0.6216617822647095},{"id":"https://openalex.org/C86745063","wikidata":"https://www.wikidata.org/wiki/Q3737406","display_name":"CYP1A2","level":4,"score":0.5658800601959229},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.5648074746131897},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.5161575078964233},{"id":"https://openalex.org/C526171541","wikidata":"https://www.wikidata.org/wiki/Q407693","display_name":"Cytochrome P450","level":3,"score":0.4983799457550049},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.48880574107170105},{"id":"https://openalex.org/C168831097","wikidata":"https://www.wikidata.org/wiki/Q413248","display_name":"Depsipeptide","level":2,"score":0.4263920485973358},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.36044949293136597},{"id":"https://openalex.org/C2778305200","wikidata":"https://www.wikidata.org/wiki/Q174378","display_name":"Histone deacetylase","level":4,"score":0.2965514063835144},{"id":"https://openalex.org/C64927066","wikidata":"https://www.wikidata.org/wiki/Q36293","display_name":"Histone","level":3,"score":0.0995965301990509},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.06021612882614136}],"mesh":[{"descriptor_ui":"D003577","descriptor_name":"Cytochrome P-450 Enzyme System","qualifier_ui":"Q000032","qualifier_name":"analysis","is_major_topic":false},{"descriptor_ui":"D003577","descriptor_name":"Cytochrome P-450 Enzyme System","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006655","descriptor_name":"Histone Deacetylases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008862","descriptor_name":"Microsomes, Liver","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D008862","descriptor_name":"Microsomes, Liver","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":true},{"descriptor_ui":"D011480","descriptor_name":"Protease Inhibitors","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011480","descriptor_name":"Protease Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D047630","descriptor_name":"Depsipeptides","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D047630","descriptor_name":"Depsipeptides","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D056572","descriptor_name":"Histone Deacetylase Inhibitors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1248/bpb.28.124","doi":"https://doi.org/10.1248/bpb.28.124","is_oa":true,"landing_page_url":"https://doi.org/10.1248/bpb.28.124","pdf_url":"https://www.jstage.jst.go.jp/article/bpb/28/1/28_1_124/_pdf","source":{"id":"https://openalex.org/S165235614","display_name":"Biological and Pharmaceutical Bulletin","issn_l":"0918-6158","issn":["0918-6158","1347-5215"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","jufo-1","medline","norway-1","poland-70","russia-white-list-2"],"host_organization":"https://openalex.org/P4310313382","host_organization_name":"Pharmaceutical Society of Japan","host_organization_lineage":["https://openalex.org/P4310313382"],"host_organization_lineage_names":["Pharmaceutical Society of Japan"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biological and Pharmaceutical Bulletin","raw_type":"journal-article"},{"id":"pmid:15635176","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/15635176","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biological & pharmaceutical bulletin","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1248/bpb.28.124","doi":"https://doi.org/10.1248/bpb.28.124","is_oa":true,"landing_page_url":"https://doi.org/10.1248/bpb.28.124","pdf_url":"https://www.jstage.jst.go.jp/article/bpb/28/1/28_1_124/_pdf","source":{"id":"https://openalex.org/S165235614","display_name":"Biological and Pharmaceutical Bulletin","issn_l":"0918-6158","issn":["0918-6158","1347-5215"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","jufo-1","medline","norway-1","poland-70","russia-white-list-2"],"host_organization":"https://openalex.org/P4310313382","host_organization_name":"Pharmaceutical Society of Japan","host_organization_lineage":["https://openalex.org/P4310313382"],"host_organization_lineage_names":["Pharmaceutical Society of Japan"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Biological and Pharmaceutical Bulletin","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9391000270843506,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2012778393.pdf","grobid_xml":"https://content.openalex.org/works/W2012778393.grobid-xml"},"referenced_works_count":23,"referenced_works":["https://openalex.org/W1496431937","https://openalex.org/W1531373906","https://openalex.org/W1765706822","https://openalex.org/W1882430758","https://openalex.org/W1992321786","https://openalex.org/W2019121117","https://openalex.org/W2035209422","https://openalex.org/W2043368734","https://openalex.org/W2052181006","https://openalex.org/W2087526401","https://openalex.org/W2094412093","https://openalex.org/W2095228162","https://openalex.org/W2097100227","https://openalex.org/W2097502628","https://openalex.org/W2113144329","https://openalex.org/W2126772533","https://openalex.org/W2131614625","https://openalex.org/W2133127743","https://openalex.org/W2153221157","https://openalex.org/W2155268095","https://openalex.org/W2164382188","https://openalex.org/W2335309823","https://openalex.org/W2511531422"],"related_works":["https://openalex.org/W2015968334","https://openalex.org/W2077770154","https://openalex.org/W2443350837","https://openalex.org/W2354971890","https://openalex.org/W2170555743","https://openalex.org/W1982204329","https://openalex.org/W1872591512","https://openalex.org/W1915424013","https://openalex.org/W2995797016","https://openalex.org/W1746765074"],"abstract_inverted_index":{"FK228":[0,29,51,65,91,93,145,175,201],"(FR901228,":[1],"depsipeptide)":[2],"is":[3,52,206],"a":[4,80,110,186],"potent":[5,187],"histone":[6],"deacetylase":[7],"inhibitor":[8],"currently":[9],"in":[10,31,42,96,177,202],"phase":[11],"II":[12],"clinical":[13],"trials":[14],"for":[15,28,64,90],"cancer":[16],"treatment.":[17],"In":[18,173],"the":[19,22,43,87,141,159,198],"present":[20],"study,":[21],"cytochrome":[23],"P450":[24,120],"(P450)":[25],"enzymes":[26],"responsible":[27],"metabolism":[30,199],"human":[32,39,97,136,178,203],"liver":[33,40,98,179,204],"microsomes":[34,41,99,180,205],"were":[35,67,77],"investigated.":[36],"Incubation":[37],"with":[38,106,118],"presence":[44],"of":[45,83,114,144,158,161,200],"an":[46,191],"NADPH-generating":[47],"system":[48],"revealed":[49],"that":[50,197],"metabolized":[53],"to":[54],"at":[55,79],"least":[56],"10":[57,84],"different":[58],"metabolites.":[59],"Km":[60,88],"and":[61,70,129,150,156,190],"Vmax":[62],"values":[63],"disappearance":[66,94,176],"20.3":[68],"microM":[69,85],"561.9":[71],"pmol/min/mg":[72],"protein,":[73],"respectively.":[74,163],"Further":[75],"studies":[76],"performed":[78],"substrate":[81],"concentration":[82],"(half":[86],"value":[89],"disappearance).":[92],"activities":[95,122],"from":[100],"12":[101],"individuals":[102],"strongly":[103],"correlated":[104],"(r2=0.957)":[105],"testosterone":[107],"6beta-hydroxylase":[108],"activities,":[109],"marker":[111],"enzyme":[112],"activity":[113,143,160,170],"CYP3A4/5,":[115],"but":[116],"not":[117],"other":[119],"enzyme-specific":[121],"(CYP1A2,":[123],"2A6,":[124],"2C8,":[125],"2C9,":[126],"2C19,":[127],"2D6,":[128],"4A).":[130],"Among":[131],"14":[132],"recombinant":[133],"heterologously":[134],"expressed":[135],"P450s":[137,165],"examined,":[138],"CYP3A4":[139,188],"exhibited":[140],"highest":[142],"disappearance.":[146],"CYP3A5,":[147],"1A1,":[148],"2B6,":[149],"2C19":[151],"showed":[152,166],"16.8%,":[153],"5.2%,":[154],"1.6%,":[155],"1.3%":[157],"CYP3A4,":[162],"Other":[164],"no":[167],"significant":[168],"metabolic":[169],"toward":[171],"FK228.":[172],"addition,":[174],"was":[181],"markedly":[182],"inhibited":[183],"by":[184,209],"ketoconazole,":[185],"inhibitor,":[189],"anti-CYP3A4":[192],"antibody.":[193],"These":[194],"results":[195],"indicate":[196],"catalyzed":[207],"mainly":[208],"CYP3A":[210],"enzymes,":[211],"particularly":[212],"CYP3A4.":[213]},"counts_by_year":[{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2018,"cited_by_count":2},{"year":2017,"cited_by_count":1},{"year":2016,"cited_by_count":2},{"year":2015,"cited_by_count":3},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":4},{"year":2012,"cited_by_count":3}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}